This proposal will continue our studies of the molecular events involved in the operation of the Na ion-dependent bile salt transport system. Bile salts, the anionic substrate for this system, will have their side chain modified in such a manner that the regular anionic side chain will be retained, but will also have in proximity the functioning moiety of the harmaline molecule. In this manner interaction with the bile salt transport system could involve the postulated anionic and cationic sites. High affinity inhibition will be anticipated, which could then be utilized, not only for pharmacological studies but as experimental probes for the further fractionation of this transport system. We also intend that the fractionation of the ileal brush border membranes which contain this transport system, will make critical use of the recent advances on immunology, which utilizes lymphocyte hybridomas to produce monoclonal antibodies.